The human skin is composed of dermis and epidermis. The dermis mainly synthesizes collagen and other proteins, and is mainly composed of fibroblasts producing a small amount of lipid. In contrast, the epidermis mainly produces lipid and is mainly composed of keratinocytes substantially not synthesizing collagen. In particular, the epidermis located at the outermost layer of the skin acts to defend against various stimulus form the outside, e.g., physicochemical stimulation factors, such as chemical substances, air pollutants, dry environment, and ultraviolet ray, and to perform a protective function of preventing excessive dissipation of moisture in the body through the skin. Such protective function may be possible by allowing stratum corneum composed of keratinocytes to be normally formed and maintained.
Stratum corneum (homey layer) existing at the outermost layer of the epidermis is formed from keratinocytes and is composed of keratinocytes having differentiation completed and a lipid layer surrounding the keratinocytes (J. Invest. Dermatol. 1983; 80: 44-49). The keratinocytes are cells formed through such a manner that base cells continuously multiplying in stratum basale are subjected to step by step morphological and functional changes while moving to stratum corneum. When a predetermined period of time is elapsed, old keratinocytes are detached from the skin and new keratinocytes moved upward from the stratum basale may substitute the function thereof, and this repetitive process of series of changes is referred to as “epidermis differentiation” or “keratinization”. In the process of keratinization, the keratinocytes form the stratum corneum while producing a natural moisturizing factor (NMF) and intercellular lipids (ceramide, cholesterol, and fatty acid) to allow the stratum corneum to have firmless and flexibility, and thus, the stratum corneum may have a function as a skin barrier that acts as an external barrier layer.
The stratum corneum may easily lose its function due to lifestyle factors such as excessive cleansing or bath, environmental factors such as dry air or pollutants, and endogenous diseases such as atopic skin or geriatric skin. In fact, hazard factors on the skin have been gradually increased in modern times, and there is a tendency for a number of people having skin, in which keratinocytes do not exhibit a normal skin barrier function, to be increased according to the fact that generation and detachment rates are decreased due to the changes in dietary habits, and the moisturizing factor and the amount of lipid in the stratum corneum are decreased due to the degradation of the function of the keratinocytes.
It has been revealed that abnormalities in the skin barrier function are the most important cause of xeroderma, regarded as one of the main diseases of modern society. Psoriasis is an inflammatory disease of the skin that is characterized by epidermal proliferation and skin inflammation, in which the skin thickens and turns red due to inflammation and scales (dead skin cells) may occur. Although it is not infectious, it looks ugly, and as a result, patients suffer from stress and degradation of quality of life. Overgrowth and inhibition of differentiation of keratinocytes (Roenigk H H, Marcel Dekker Inc., pp. 233-247, 1985), and abnormalities in the immune system associated with white blood cells, such as T cells or dendritic cells, (J. C. Prinz, Clinical and Experimental Dermatology, 24, 291-295, 1999) have been proposed as causes of the onset of psoriasis. Atopic dermatitis that recently occurs in 10% of children is a chronic recurrent eczematous disease and pathogenesis thereof is not clear. However, the main symptoms thereof include chronic xeroderma and resulting damage to the skin barrier, and if without proper care, atopic dermatitis may develop into lesions such as lichenification, pigmentary changes, and erythroderma. Also, a phenomenon of skin atrophy, occurring in the case of using steroids excessively or over a prolonged period of time, is a side effect in which the skin becomes thinner and the functions thereof are weakened, and it has been reported that the main causes thereof include an inhibition of fibroblast activity and a decrease in the generation of collagen due to steroids (S. Hammer et. al., J. Cell. Biochem, 91, 840-851, 2004).
Typically, for this purpose, a method of increasing moisture retention in the stratum corneum has been performed by using humectants having moisture absorbing properties or occlusive moisturizers preventing evaporation of moisture. Examples of the humectants may be glycerin, propylene glycol, 1,3-butylene glycol, polyethylene glycol, sorbitol, and sodium 2-pyrrolidone-5-carboxylate. However, there may be severe stickiness or may be pultaceous when being applied to the skin. Lipid components, such as ceramide, or essential fatty acids and lipid complexes have been used as occlusive moisturizers (J. Invest. Dermatol. (5), 731-740, 1994), but it may be difficult to maintain stability of emulsified formulations and may not be suitable for preparing transparent gel products. Also, in the case that the foregoing moisturizers having typical moisture retention functions are used, temporary relief of symptoms may be anticipated, but fundamental healing may be difficult. Therefore, there is an urgent need to develop a material fundamentally regenerating the damaged barrier by promoting the differentiation of keratinocytes and the growth of fibroblasts.
Meanwhile, as claims, in which the differentiation of keratinocytes is important to prevent drying of moisture in the skin, have recently been raised, it was found that stratum corneum may play a role as a moisture retention barrier of the skin when a process of differentiation, in which keratinocytes of stratum basale develop into keratinocytes of the outermost stratum corneum, must be normally performed. That is, cells may generate a natural moisturizing factor (NMF) and intercellular lipids during the process of keratinization. As a result, the stratum corneum becomes firm and flexible, and thus, may function as a protective barrier. When physiologically considering the tendency in which the skin dries as the age of a person increases, it may be interpreted that time required for the detachment of stratum corneum is increased or ability of epidermal cells for synthesizing lipids is decreased, and the moisturizing factor and the amount of lipids in the stratum corneum are decreased. Therefore, a new approach able to improve functions of moisture retention and protection from the external environment may be possible by inducing the strengthening of the skin barrier through the promotion of the differentiation of keratinocytes.